Contribution of pathogenic T helper 1 and 17 cells to bursitis and tenosynovitis in polymyalgia rheumatica

BackgroundAlthough polymyalgia rheumatica (PMR) is a very common rheumatic inflammatory disease, current insight into the pathobiology of PMR is limited and largely based on studies in blood. We investigated T helper 1 (T-H1) and T helper 17 (T-H17) cell responses in blood, synovial fluid and bursa tissue of patients with PMR. Materials and methodsBlood samples were collected from 18 patients with new-onset PMR and 32 healthy controls. Synovial fluid was aspirated from the inflamed shoulder bursae or biceps tendon sheath of 13 patients. Ultrasound-guided biopsies of the subacromial-subdeltoid (SASD) bursa were obtained from 11 patients. T cells were examined by flow cytometry, immunohistochemistry and immunofluorescence staining. ResultsBesides an increase of T-H17 (CD4(+)IL-17(+)IFN-gamma(-)) cells and T cytotoxic 17 (T-C17; CD8(+)IL-17(+)IFN-gamma(-)) cells, no other major changes were noted in the circulating T cell compartment of patients with PMR. Absolute numbers of CD4(+) and CD8(+) T cells were similar in blood and synovial fluid of patients with PMR. Synovial fluid T cells showed an effector-memory (CD45RO(+)CCR7(-)) phenotype. Percentages of T-H1 (CD4(+)IFN-gamma+IL-17(-)) cells and T-H1/T-H17 (CD4(+)IFN-gamma+IL-17(+)) cells, but not T-H17 or T-C17 cells, were increased in the synovial fluid. Bursa tissue biopsies contained a small number of T cells, which were mostly CD8 negative. The majority of bursa tissue T cells produced IFN-gamma but not IL-17. For comparison, B cells were scarcely detected in the bursa tissue. ConclusionAlthough the circulating T-H17 cell pool is expanded in patients with PMR, our findings indicate that T-H1 cells are involved in the inflammation of bursae and tendon sheaths in this condition. Our study points towards the T-H1 cell pathway as a potential target for therapy in PMR.